Geographic analysis of RKIP expression and its clinical relevance in colorectal cancer

Kölzer, V.; Karamitopoulou, E.; Dawson, Heather; Kondi-Pafiti, A.; Zlobec, I.; Lugli, A. (2013). Geographic analysis of RKIP expression and its clinical relevance in colorectal cancer. British journal of cancer, 108(10), pp. 2088-2096. Nature Publishing Group 10.1038/bjc.2013.197

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BACKGROUND This study evaluates the geographic expression pattern of Raf-1 Kinase Inhibitor Protein (RKIP) in colorectal cancer (CRC) in correlation with clinicopathological and molecular features, markers of epithelial-mesenchymal transition (EMT) and survival outcome. METHODS Whole-tissue sections of 220 well-characterised CRCs were immunostained for RKIP. NF-κB and E-Cadherin expression was assessed using a matched multi-punch tissue microarray. Analysis of mismatch repair (MMR) protein expression, B-Raf and KRAS mutations was performed. RKIP expression in normal mucosa, tumour centre, invasion front and tumour buds was each assessed for clinical relevance. RESULTS RKIP was diffusely expressed in normal mucosa and progressively lost towards tumour centre and front (P<0.0001). Only 0.9% of tumour buds were RKIP-positive. In the tumour centre, RKIP deficiency predicted metastatic disease (P=0.0307), vascular invasion (P=0.0506), tumour budding (P=0.0112) and an invasive border configuration (P=0.0084). Loss of RKIP correlated with NF-κB activation (P=0.0002) and loss of E-Cadherin (P<0.0001). Absence of RKIP was more common in MMR-deficient cancers (P=0.0191), while no impact of KRAS and B-Raf mutation was observed. RKIP in the tumour centre was identified as a strong prognostic indicator (HR (95% CI): 2.13 (1.27-3.56); P=0.0042) independently of TNM classification and therapy (P=0.0474). CONCLUSION The clinical relevance of RKIP expression as an independent prognostic factor is restricted to the tumour centre. Loss of RKIP predicts features of EMT and correlates with frequent distant metastasis.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Kölzer, Viktor; Karamitopoulou, Evanthia; Dawson, Heather; Zlobec, Inti and Lugli, Alessandro


500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health




Nature Publishing Group




Andrea Arnold

Date Deposited:

03 Apr 2014 14:17

Last Modified:

13 Feb 2017 10:04

Publisher DOI:


PubMed ID:





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